DE1642065C3 - Antimicrobial means - Google Patents

Description

in which Y is chlorine or a nitro group, η the numbers O to 2, R is hydrogen or a methyl radical, B is hydrogen, a methyl radical, an ethyl radical or a phenylcarbamic acid ester group of the formula

Y ₁ , '

I-C-O-CH

Il I

O H

represents, characterized by a content of dimethyl sulfoxide and ethanol or isopropanol.

2. Antimicrobial agents according to claim I, characterized in that they contain the bromo-nitroalkyl-N-phenyl-carbamate in an amount of 0.05-5 % By weight, preferably 0.1-1.0% by weight.

3. Antimicrobial agents according to claim 1 and 2, characterized in that they are ethanol or Isopropanol in an amount of 5-30% by weight, preferably 10-20% by weight.

Λ Antimicrobial agents according to claim I to 3, characterized in that they contain dimethyl sulfoxide in an amount of 10-50% by weight, preferably 20-40% by weight.

represents.

Such agents are effective against both gram-positive and gram-negative bacteria, even in low concentrations, and can also be used with Use success as fungicides. Even if the soldering effect of these agents is guaranteed in low concentrations, it requires in in some cases longer periods of time that are not available in some types of application.

The invention is therefore based on the object of reducing the effectiveness of these antimicrobial agents in such a way

The subject of patent 16 68 195 are antimicrobial agents containing bromo-nitroalkyl-N-phenyl-carbamates of the formula

NO ₂ -NH-C-O-CH-C-Br

Il I!

ORB

in which Y is chlorine or a nitro group, η the numbers 0 to 2, R is hydrogen or a methyl radical, B is hydrogen, a methyl radical, an ethyl radical or a phenylcarbamic acid ester group of the formula

-NH-C-O-CH

to improve that even within a very short time safe killing of microorganisms is guaranteed

According to the invention, this object is achieved in that antimicrobial agents based on bromo-nitroalkyl-N-phenyl-carbamates of the general formula mentioned above and containing dimethyl sulfoxide and ethanol or isopropanol are used

The bactericidal and fungicidal substances on which the antimicrobial agents according to the invention are based are in principle all bromo-nitroalkyl-N-phenylcarbamates, those of the general ones mentioned Formula match.

Bromo-nitroalkyl-N-phenylcarbamates, which are bactericidal and fungicidal substances in question e.g.

2-Bromo-2-nitroethyl-N- (3-chlorophenyl) -caroaniate I-methyl ^ -bromo ^ -nitroethyl-N-phenylcarbamate 2-Bromo-2-nitrophenyl-N- (3-chlorophenyl) -carbsmat

2-Bromo-2-nitrobutyl-N-phenylcarbamate 2-bromo-2-nitrobutyl-N- (3,4-dichlorophenyl) -

carbamate, 1-methyl-2-bromo-2-nitropropyl-N- (4-nitro-

phenyl) carbamate

l-methyl-2-bromo-2-nitrobutyl-N-phenyl-carbamate 2-bromo-2-nitropropanediol- (13) -bis-N-phenyl-

carbamate 2-bromo-2-nitrpropanediol- (l, 3) -bis-N- (3-chloro-

phenyl) -carbaTnat, 2-Bromo-2-nitropropanediol- (13) -bis-N- (3,4-di-

chlorophenyl) carbamate 2-bromo-2-nrtro-propanediol- (l, 3) -bii-N- (4-nitro-

phenyl) carbamate l-methyl-2-bromo-2-nilropropanediol- (1,3} -bis-N-

(3-chlorophenyl) carbamate l3-Dimethyl-2-bromo-2-nitropropanediol- (13) -bis-

N- (3,4-dichlorophenyl) carbamate.

The preparation of the bromo-nitroalkyl-N-phenylcarbamates can be carried out in a manner known per se Addition of the corresponding nitro alcohols or substituted bromo-nitro alcohols to phenyl isocyanate or substituted by chlorine or a nitro group Phenyl isocyanate. For this purpose, 0.1 Moles of the nitro alcohol with 0.12 moles of the isocyanate in anhydrous benzene under reflux for 4-5 hours heated. After most of the benzene has been distilled off, the bromo-nitroalkyl-N-pi; rnylcarbamate can isolated and recrystallized from a solvent mixture benzene / benzir 1: 1.

Due to the simultaneous presence of ethanol or isopropanol and dimethyl sulfoxide in addition to the aforementioned bromo-nitro-alkyl-N-phenylcarbamates in the antimicrobial agents according to the invention are surprisingly effective in killing them very substantially improved. With the combinations according to the invention, killing times are achieved achieved the use of the bromo-nitroiilkyl-N-phenyl-

M) carbamate also used in antimicrobial agents only Appear short application times, in which they would not be sufficiently effective on their own.

The content of bromo-nitroalkyl-N-phenylcarbamates in antimicrobial agents is 0.05-5% by weight,

μ preferably 0.1-1% by weight.

The ethanol or isopropanol content of the antimicrobial agents is 5-30% by weight, preferably 10-20% by weight and dimethyl sulfoxide should be in them

an amount of 10-50% by weight, preferably 20-40 % By weight.

In preparations in which an addition of complexing agents is appropriate, the inventive Combination also with complexing agents, which in the Hampshire test have a calcium carbonate binding capacity greater than 230 mg per g complexing agent, be combined. This enables a further increase in effectiveness.

The antimicrobial combinations of bromo-nitroalkyl-N-phenylcarbamates, ethanol or isopropanol and dimethyl sulfoxide can be used as detergents and disinfectants for hands and instruments as well as antimicrobial tinctures and sprays for combating skin fungi and the like. Use.

The subject matter of the invention is explained in more detail by the following examples.

The ablation concentrations and times of the Individual substances as well as the combinations were with Determined with the help of the quantitative suspension test This test represents a modified version of that described in the guidelines for testing chemical Disinfectant of the German Society for Hygiene and Microbiology (1959) specified suspension test to determine the bactericidal, fungicidal and sporicidal effects.

0.1 ml of the germ suspension were pipetted into small Petri dishes at room temperature of 18-21 ° C To this end, 10 ml of the various dilutions of the products to be tested were added. After the The intended exposure times were 0.1 mf of material with each of the disinfectant-germ mixtures taken from a sterile pipette and in the case of bacteria on the surface of Bouillo.i agar plates, in the case of yeast or fungi on the surface of wort-agar plates evenly distributed by carefully swirling. The withdrawals were made in the following time intervals: 30 seconds, 1, 3, 5 and 10 minutes. To eliminate bactericidal aftereffects, the bouillon and the wort contained one Addition of 3% polyoxyethylene sorbilane monooleate (Tween 80) and 03% lecithin. This procedure has in addition to the more favorable conditions for mushrooms

Table 1

The advantage is that you can not only determine growth or sterility (endpoint method), as is the case with inoculation in liquid nutrient media, but also determine the number of surviving organisms semi-quantitatively by counting the colonies that have grown. Subsequent to the inoculation on the nutrient medium plates, it was determined with which concentrations and in which times the germs could be killed. For this purpose, the plates were incubated at 37 ° C in the case of bacteria and at 30 ⁰ C in the case of yeasts and fungi and then macroscopically examined for growth and the incubation was in the case of using Epidermophyton Kaufmann-Wolf 21 days in the other test organisms 8 Days. The incubation period of 21 days for Epidermophyton Kaufmann-Wolf was chosen on the basis of the guidelines mentioned above, because when evaluating disinfectants against skin fungi, an agent is considered suitable if the growth the fungi is delayed by at least 21 days after a certain period of exposure to the agent.

If there was no alcohol in the product to be tested, the nitroalkyl-N-phenyl-carbamates to be tested were made from a solution containing acetone brought in

As the antimicrobial agents of the present invention The following bromo-nitroalkyl-N-phenylcarbamates were investigated on the underlying active substances

A 2-Bromo-2-nitro-butyl-N-phenyl-carbaxnate B 2-bromo-2-nitro-butyl-N- (3,4-dichlorophenyl) -

carbamate C 2-bromo-2-nitro-propanediol- (13) -bis-N-phenyl-

carbamate D 2-bromo-2-nitro-propanediol- (l _r 3) rbis-N- (3,4-di-

chlorophenyl) carbamate

The test germs used were: Staphylococcus aureus, Escherichta coli, Pseudomonas zsruginosa, Candida albicans, Epidermophyton Kaufmann-Wolf, Aspergillus niger, Penicillium cameruncnse.

The kill concentrations and kill times listed in the tables below were determined in these plate tests.

Combinations of substances

Substance active substance A

Sta aur

ui

Active ingredient B

erg.

3 ¹ p

Sta. aure

Pse
mon

Candi

perg.

Ep

Isopropanol Dimethyl sulfoxide

Active ingredient

Isopropanol

DMSO

Isopropanol

DMSO

Isopropanol

Active ingredient

Isopropanol Active ingredient

isopropanol Active ingredient

IO 20th

40

0.1 0.5

IO 40 2Ö 40 10

⁰ 1 0.1 /

10 0

20 1 0.1 [

continuation

Substance combinations

Substance active substance A Active ingredient B

«Λ - U [β u U

3 "5 ό S Ή ^u

S ⁸ . 1 | § 1

α Ul CU E U UJ

ε?

& g

<B,

3 C C

«Ο S

α! ε υ

"Ξ" S W

Isopropane
Active ingredient 20th
0.5 / DMSO
Active ingredient 40 1
ο, ι / DMSO
Active ingredient 40 1
0.5 / Isopropanol
DMSO
Active ingredient ρ ο ο Isopropanol
DMSO
Active ingredient 10)
40 \
0.5] Isopropanol
DMSO
Active ingredient 20]
40 \
ο, ι J Isopropanol
DMSO
Active ingredient 20th
40 }
0.5

0.5 0.5 0.5 0.5 0.5 10 5 0.5 1 1 Ϊ 0.5 5 5

1 0.5 0.5 3 0.5>> 1 0.5 0.5 1 0.5> 10

0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 0.5 1 0.5

Specification of the killing times in minutes

> = no destruction within 10 minutes

Test temperature 20 "C Table 2

Combinations of substances

Table 3

substance

Isopropanol 10
20th Dimethyl sulfoxide 40 (DMSO) Active ingredient 0.5 Isopropanol 10 1 DMSO 40 y Isopropanol 20 1 DMSO 40 y Isopropanol 10 1 Active ingredient 0.5 / Isopropanol 20 1 Active ingredient 0.5 / DMSO 40 1 Active ingredient 0.5 / Isopropanol 10 I. DMSO 40 Active ingredient 0.5 y Isopropanol 20th DMSO 40 Active ingredient 0.5

substance substance A. ΙΛ O
ui B. to . ^ _- combinations 'aureu yeah aureu ο
CJ
ui (%) I Sta. Sia.

0.5

Specification of the killing times in minutes > = no destruction within 10 minutes Test germ: Staphylococcus aureus SG 511 Test temperature: 20 C

Isopropanol 20 Dimethyl IO

sulfoxide 20

(DMSO) 30

Active ingredient 0.5 Isopropanol 20

DMSO 10

Isopropanol 20

DMSO 20

Isopropanol 20

DMSO 30

Isopropanol 20 Active ingredient 0.5

DMSO 10

«) Active ingredient 0.5

DMSO 20

Active ingredient 0.5

DMSO 30

Active ingredient 0.5 Isopropanol 20

DMSO 10

Active substance

VVV

VVV

VVV

10

10

continuation

substance substance A. IA O
U B. regret CO combinations regret UJ ■ 73 LU £ 3 (%) t / l to

Isopropanol DMSO active substance

Isopropanol DMSO active substance

20 20

0.5

20 30 0.5

5 1

I.

0.5

Specification of the killing times in minutes> = no killing within 10 minutes Test temperature: 20 ° C

Tabel

Substance combinations substance

Ethanol

Dimethyl sulfoxide (DMSO) active ingredient ethanol DMSO ethanol DMSO Ethanol Active Ingredient Ethanol Active Ingredient DMSO Active Ingredient Ethanol DMSO active ingredient Ethanol DMSO active ingredient

10 20

40

0.5

10 40

20 40

10

20th

0.5 /

40 I.

10

10 40

0.5 20} 40

0.5 y

0.5

0.5 lean use kills the test germs in reach in a short time. Even the combination of two components does not bring about any noteworthy change of the test results. Only when all three components are used according to the invention are the draining times surprisingly extremely reduced.

Compositions for some antimicrobial agents are given below.

Antimicrobial solution
2-bromo-2-nitro-butyl-N-phenyl-

carbamate 0.5 part by weight c

Isopropanol 20.0 part by weight c

Dimethyl sulfoxide 30.0 part by weight c

Water 50.0 part by weight c

Hand disinfectant

2-B-oiTi-2-nitro-but "! - N '34 d;

chlorophenyl carbaniate (). "> Parts by weight

Ethanol 20.0 part by weight c

Dimethyl sulfoxide 30.0 parts by weight

Sodium Lauryl Sulphate 7.5 parts by weight

Coconut fatty acid monoethanolamide 0.5 part by weight

Nitrilotriacetic acid 2.0 parts by weight

Water 40.0 parts by weight

Disinfectant for instruments
2-bromo-2-nitro-propanediol

(1,3) -bis-N- (3.4-dichlorophenyl) -

carbamate 0.5 part by weight

Isopropanol 20.0 parts by weight

Dimethyl sulfoxide 30.0 parts by weight

ivArninoethane-ft.rt-diphosphon-

acid 10.0 parts by weight

Water 40.0 parts by weight

Antimicrobial tincture

(mainly against bacterial mycoses)

2-bromo-2-nitro-butyl-N-phenyI-

carbamate 0.5 part by weight

Ethanol 20.0 parts by weight

Dimethyl sulfoxide 40.0 parts by weight

Hydrocortisone 0.5 part by weight

Water 40.0 parts by weight

45

Indication of the death rate in minutes like this

> = no killing within 10 minutes Test germ: Staphylococcus aureus SG test temperature. 20 ^c C

As can be seen from the tables above, neither can the alcoholic component nor by dimethyl sulfoxide (DMSO) nor by the bromo-nitroalkyl-N-phenylcarbamate used in al-antimicrobial spray

2-bromo-2-nitro-butyl-N- (3,4-di-

chlorophenyl) carbamate
Isopropanol
Dimethyl sulfoxide
water
Propellant

0.5 part by weight

25.0 parts by weight

20.0 parts by weight

55.0 parts by weight

100.0 parts by weight

The advantage that can be achieved with the agents according to the invention is that you can use them within A killing of gram-positive and gram-negative bacteria as well as yeast and fungi in a very short time achieved

Claims (1)

Patent claims: I. Antimicrobial agents according to patent 16 68 195 based on bromo-nitroalkyl-N-phenyl carbonates the formula NO ₂ H-C-O-CH-C-Br Il I I ORB